Therapeutic Plasmapheresis

Therapeutic Plasmapheresis

What is the Therapeutic Plasmapheresis

Therapeutic plasmapheresis is an extracorporeal blood purification technique designed for the removal of pathogenic substances from the plasma of patients. Examples of these substances include pathogenic autoantibodies, immune complexes, cryoglobulins and cholesterol-containing lipoproteins.

Possibilities of Plasma Apheresis

Removal of antibodies

Alloantibodies

Autoantibodies

Immune Complexes

Removal of excessive or abnormal substances

Paraproteins

Cholesterol in Hypercholesterolaemia

Removal of toxins

Protein-bound Drugs / Toxins

Mushroom Poisons

Modalities of therapeutic plasmapheresis

Therapeutic plasmapheresis includes the following three modalities.

Plasma Exchange (PE)

Double Filtration Plasmapheresis (DFPP)

Immunoadsorption (IA) / Plasma Adsorption (PA)

Applies diseases for plasmapheresis

In certain conditions, we may consider include this intervention in the individualized treatment plan. The procedure will help to quickly remove the disease mediators and help to improve the patient's condition in short term, while encouraging the patient to participate in long term therapeutic lifestyle changes to cure the illness root causes.

Plasmapheresis is an applicable form of treatment for many types of diseases, including autoimmune disorders and certain types of cancer. The main goal of this treatment is to remove aberrant antibodies or protein, thereby preventing the antibodies from attacking their targets and removing the protein accumulation that is impairing certain body systems. Example of diseases;

Myasthenia gravis(MG)

Lambert-Eaton Syndrome

Guillain-Barré syndrome (GBS)

Chronic inflammatory demyelinating polyneuropathy(CIDP)

Thrombotic thrombocytopenic purpura (TTP)

Goodpasture's Syndrome

Multiple Myeloma

Familial hypercholesterolemia (FH)

Arteriosclerosis obliterans (ASO)

Pemphigus

Pemphigoid

Toxic epidermal necrolysis (TEN)

Chronic hepatitis C

Primary macroglobulinemia

Cryoglobulinemia

ABO-mismatched renal transplantation

Allogeneic renal transplantation

Rapidly progressive glomerulonephritis (RPGN)

Henoch-Schönlein purpura nephritis

Systemic lupus erythematosus (SLE)

Arteriosclerosis obliterans (ASO)

Focal glomerulosclerosis

Multiple sclerosis (MS)

Miller-Fisher syndrome (MFS)

Severe blood-type incompatible pregnancy

Age-related macular degeneration(AMD)

Systemic lupus erythematosus (SLE)

Rheumatoid arthritis(RA)with vasculitis

Myasthenia Gravis

This disease is caused by the production of IgG antibodies (antiacetylcholine receptor antibodies) that attack the acetylcholine receptors of skeletal muscles. These antibodies cause a decrease in the amount of acetylcholine receptors and ultimately decreases the action potential achieved with stimulation. Myasthenia Gravis is characterized by muscular weakness and fatigue, and occurs with the highest prevalence in women in their 20s and 30s.

Plasmapheresis is generally incorporated in a patient’s treatment regime when their symptoms are severe. Although there is not a lot of literature on this subject, the decrease of circulating antireceptor antibodies by plasmapheresis has been shown to improve the ability of muscle fibers to contract. Improvement may be apparent within 1 day of treatment or it may take a week, and the improvement will only last for about 2 to 4 weeks if immunosuppressive drugs are not taken to prevent antibodies from reforming. Generally patients only undergo 2 to 5 plasmapheresis treatments, but some may need long-term maintenance plasmapheresis.

Lambert-Eaton Syndrome

This Myasthenia Gravis-like disorder is characterized by a disturbed communication between nerves and muscles caused by an immune attack on the neuromuscular junction. Most patients with this disorder present around the age of 40 to 79 years of age, and typically exhibit the following symptoms: muscle weakness, hyporeflexia and autonomic dysfunction. The hallmark of Lambert-Eaton syndrome is the presence of antibodies directed at voltage-gated calcium channels, essential for neurotransmitter release.

Therapeutic plasma exchange is used in the treatment of this disorder by removing the antibodies directed at the voltage gated calcium channels. However, therapeutic plasma exchange has been shown to cause detrimental effects on a patient’s health if not used in conjunction with immunosuppressive therapy. Therefore, therapeutic plasma exchange is predominantly used in patients with severe or rapidly progressing neurological deficits, or in patients too uncomfortable to wait for the immunosuppressive drugs to take effect. Plasmapheresis sessions are commonly carried out 5 to 15 times a day over the course of 5 to 19 days or 8 to 10 times a day over the course of 5 to 7 days. Due to the slow turnover of the presynaptic voltage gated calcium channels in comparison to the postsynaptic acetylcholine receptors, it may take two or more weeks after the initiation of the plasmapheresis treatment before any improvement is seen.

Guillain-Barré Syndrome

This disorder is also known as acute inflammatory demyelinating polyneuropathy and is of an unknown etiology; however it commonly occurs after an acute upper respiratory infection. The presence of antibodies to the myelin sheath and the fact that many patients present with this disease after overcoming an infectious illness, suggests cross-reactive antibodies may be an important component in the development of this disease. This syndrome only affects the peripheral nervous system, leading to inflammation and degeneration of nerve roots and ganglia. It is thought that the tissue damage associated with this disease may be caused by the binding of proinflammatory molecules. Some symptoms associated with this disease are symmetrical muscle weakness, and variability in blood pressure and heart rate. The majority of patients experience spontaneous recovery.

Plasmapheresis is the standard therapy in the acute stage of this disease to remove IgM antiperipheral nerve myelin antibodies and IgG anti ganglioside antibodies. Therapeutic plasma exchange was the first form of therapy used to treat Guillain-Barré syndrome that improved overall clinical outcome. Typically 250 ml of patient plasma per kg body weight over 10 to 14 days is exchanged, which is roughly equivalent to 5 to 6 therapeutic plasma exchange procedures.

Chronic Inflammatory Demyelinating Polyradiculoneuropathy

CIDP is a relatively rare disorder affecting about 1 in 100,000 adults per year. The distinguishing characteristic of CIDP is symmetrical weakness of the proximal and distal muscles, which may or may not be accompanied by numbness. These symptoms may persist for a few months, followed by cyclic healthy progression and sudden relapse. Patients with this disorder also experience neurological deficits such as decreased sensation, slowed or absent reflexes, a high level of cerebrospinal fluid protein and evidence of demyelination of their neurons. CIPD is the chronic form of Guillain-Barré syndrome.

Like Guillain-Barré syndrome, it is assumed that the cause of CIDP is autoimmune damage to the peripheral nerves. Therefore, the goal of plasmapheresis is to remove these aberrant antibodies. The majority of CIDP patients respond very well to initial therapy, but many may still need maintenance therapy including plasmapheresis as a result of their periodic relapses.

Thrombotic Thrombocytopenic Purpura (TTP)

TTP is a systemic thrombotic illness. The key pathogenic trigger of TTP is either the presence of a procoagulant factor or the absence of an antithrombotic factor, which has lead to controversy in the past as to whether the first line of treatment should be plasmapheresis to remove procoagulants, or plasma infusion to supply the patient with the absent antithrombotic factor. Plasmapheresis is currently the treatment of choice for TTP, with 80 percent of patients having a beneficial response. TTP is associated with severe deficiency of ADMTS13 enzyme, which is a protease that cleaves von Willebrand Factors, a blood glycoprotein. Idiopathic acquired TTP is sometimes associated with the presence of antibodies that bind ADMTS13, which neutralizes the protease activity. Congenital TTP is associated with somatic mutations that greatly decrease the functionality of ADMTS13.

The use of therapeutic plasma exchange as a treatment modality for TTP has reduced the mortality rate from 100 percent to less than 10 percent. The hypothesized rationale for this great success is that plasmapheresis removes the anti-ADAMTS13 antibodies, while restoring ADAMTS13 protease activity. Plasmapheresis is generally preformed daily until the patient improves.

Goodpasture’s Syndrome

This rare disease, also known as anti-glomerular basement membrane disease, primarily affects the lungs and kidneys, leading to rapid renal failure. Common symptoms associated with Goodpasture’s syndrome are fatigue, nausea, difficulty breathing, paleness, coughing up of blood and a burning sensation during urination. This disease is most prevalent in males from the age of 20 to 70 and has a 10 percent mortality rate. Goodpasture’s syndrome may last for a few weeks to 2 years, and the hallmark of this disorder is the presence of anti-glomerular basement membrane (anti-GBM) antibodies. This antibody is directed toward the α3 chain of type IV collagen, which is found in the basement membrane of renal and alveolar cells.

Plasmapheresis has greatly improved patient survival and overall renal function. Generally 4 plasma exchange sessions (1 liter each) are administered daily or every other day for 2 to 3 weeks or until the patient has improved and serum anti-GBM antibodies are no longer detectable. However it is believed that patients on dialysis prior to presenting with Goodpasture’s syndrome do not benefit from plasmapheresis, and should, therefore, only be performed on such a patient if they also present with pulmonary hemorrhage.

Multiple Myeloma

This is a relatively rare disease that is not autoimmune in nature. This form of cancer is caused by the overproduction of immunoglobulin peptides. These immunoglobulin light chains accumulate to such a high level that they end up obstructing the kidney tubules, resulting in distal tubule cast formation toxicity and ultimately renal failure.

Plasmapheresis has been shown to be extremely effective in rapidly reducing the circulating levels of these toxic immunoglobulin light chains, which reduces the risk of cast formation. In spite of the successful and rapid removal of these immunoglobulin peptides with plasmapheresis, the ultimate determinate of survival is how well a patient responds to the chemotherapy. Therefore, plasmapheresis is primarily used as a short term adjunct to chemotherapy, with sessions occurring daily or every other day for an average of 2 to 4 weeks.

Familial Hypercholesterolemia

Familial hypercholesterolemia is a rare genetic disorder that causes mutations of apo-B receptors in hepatocytes (liver cells), which results in decreased low-density lipoprotein (LDL) removal by the liver. LDL is responsible for transporting cholesterol into the liver, and is widely known as the "bad" cholesterol. If untreated, cardiovascular disease is likely to develop.

Plasmapheresis has been employed since the late 1970s in order to reduce cholesterol levels in patients with familial hypercholesterolemia, as LDL can be effectively removed by a membrane system. A single plasmapheresis treatment has been shown to decrease LDL levels by 50 to 60%. Long-term plasmapheresis treatment has also been shown to significantly decrease major adverse coronary events. These long-term treatments are usually in the form of maintenance plasmapheresis, with the ultimate goal of maintaining a lowered LDL level.

Sources:

Szczepiorkowski Z et al. Guidelines on the Use of Therapeutic Apheresis in Clinical Practice – Evidence-Based Approach from the Apheresis Applications Committee of the American Society for Apheresis. Journal of Clinical Apheresis 2007; 22.